Interleukin-11 promotes T cell polarization and prevents acute graft-versus-host disease after allogeneic bone marrow transplantation

J Clin Invest. 1998 Jul 1;102(1):115-23. doi: 10.1172/JCI3132.

Abstract

Administration of IL-11 prevented lethal graft-versus-host disease (GVHD) in a murine bone marrow transplant (BMT) model (B6 --> B6D2F1) across MHC and minor H antigen barriers (survival at day 50: 90 vs 20%, P < 0.001). Surpisingly, IL-11 administration polarized the donor T cell cytokine responses to host antigen after BMT with a 50% reduction in IFNgamma and IL-2 secretion and a 10-fold increase in IL-4. This polarization of T cell responses was associated with reduced IFNgamma serum levels and decreased IL-12 production in mixed lymphocyte cultures (MLC). In addition, IL-11 prevented small bowel damage and reduced serum endotoxin levels by 80%. Treatment with IL-11 also reduced TNFalpha serum levels and suppressed TNFalpha secretion by macrophages to LPS stimulation in vitro. IL-11 thus decreased GVHD morbidity and mortality by three mechanisms: (a) polarization of donor T cells; (b) protection of the small bowel; and (c) suppression of inflammatory cytokines such as TNFalpha. We conclude that brief treatment with IL-11 may represent a novel strategy to prevent T cell-mediated inflammatory processes such as GVHD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Bone Marrow Transplantation*
  • Cell Polarity
  • Cells, Cultured
  • Female
  • Graft vs Host Disease / prevention & control*
  • Interferon-gamma / blood
  • Interleukin-11 / pharmacology*
  • Interleukin-12 / biosynthesis
  • Intestine, Small / drug effects
  • Lipopolysaccharides / blood
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes / drug effects*
  • Transplantation, Homologous
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Interleukin-11
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • Interferon-gamma